chr17-19742099-C-T

Variant names:

• chr17-19742099-C-T
• rs57633837
• NM_000691.5:c.594G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000691.5(ALDH3A1):​c.594G>A​(p.Thr198Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,613,980 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (50 hom.)
• Consequence: ALDH3A1 NM_000691.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.745
• Publications: 3 publications found

Genes affected

ALDH3A1 (HGNC:405): (aldehyde dehydrogenase 3 family member A1) Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 17-19742099-C-T is Benign according to our data. Variant chr17-19742099-C-T is described in ClinVar as Benign. ClinVar VariationId is 710460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.745 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2139/152222) while in subpopulation AFR AF = 0.0431 (1791/41514). AF 95% confidence interval is 0.0415. There are 47 homozygotes in GnomAd4. There are 1011 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000691.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A1	NM_000691.5	MANE Select	c.594G>A	p.Thr198Thr	synonymous	Exon 5 of 11	NP_000682.3
	ALDH3A1	NM_001135167.1		c.594G>A	p.Thr198Thr	synonymous	Exon 5 of 11	NP_001128639.1	P30838
	ALDH3A1	NM_001135168.1		c.594G>A	p.Thr198Thr	synonymous	Exon 4 of 10	NP_001128640.1	P30838

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A1	ENST00000225740.11	TSL:1 MANE Select	c.594G>A	p.Thr198Thr	synonymous	Exon 5 of 11	ENSP00000225740.6	P30838
	ALDH3A1	ENST00000457500.6	TSL:1	c.594G>A	p.Thr198Thr	synonymous	Exon 4 of 10	ENSP00000411821.2	P30838
	ALDH3A1	ENST00000905965.1		c.594G>A	p.Thr198Thr	synonymous	Exon 5 of 11	ENSP00000576024.1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2133 AN: 152104 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00551 AC: 1384 AN: 251008 AF XY: 0.00447

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.00851

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00115

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00266 AC: 3886 AN: 1461758 Hom.: 50 Cov.: 32 AF XY: 0.00250 AC XY: 1818 AN XY: 727176

African (AFR) AF: 0.0450 AC: 1507 AN: 33478

American (AMR) AF: 0.00830 AC: 371 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0137 AC: 359 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000626 AC: 54 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5768

European-Non Finnish (NFE) AF: 0.00103 AC: 1148 AN: 1112006

Other (OTH) AF: 0.00619 AC: 374 AN: 60394

GnomAD4 genome AF: 0.0141 AC: 2139 AN: 152222 Hom.: 47 Cov.: 32 AF XY: 0.0136 AC XY: 1011 AN XY: 74416

African (AFR) AF: 0.0431 AC: 1791 AN: 41514

American (AMR) AF: 0.0108 AC: 165 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 68004

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.00575 Hom.: 23

Bravo AF: 0.0165

Asia WGS AF: 0.00837 AC: 30 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00202

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.1
DANN	Benign	0.86
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57633837; hg19: chr17-19645412;